Environmental factors in animal facilities can cause distress if not properly controlled. Noise is particularly important because it has non-auditory effects that alter the physiology of the whole body. Studies on the effect of low-frequency sounds on rodents have established that both physiological and behavioral responses are common. A stress response in rats is produced, as indicated by a rapid transient increase in plasma corticosterone, and gastrointestinal, cardiac and immunological functions are also affected. Rats are extremely sensitive to sounds in the ultrasonic range (12-40kHZ) and these are routinely encountered in animal facilities. It is likely that ultrasound has similar effects, but no data are available. It is essential that environmental stressors in animal facilities are minimized, not only for animal welfare, but because the results of biomedical research depend on the animals showing standard responses to clearly defined experimental procedures. The purpose of this study is to test the hypothesis that: exposure of research rats to daily periods of ultrasound affects gastrointestinal and cardiac function and that antioxidants reduce these effects. The applicant's long-term goal is to convince scientists to demand better environments for their animals. The specific aims of this study are to: 1. Determine whether subjecting rats to a short period of daily ultrasound increases: a) Production of reactive oxidant species (ROS) in the intestinal mucosa, and epithelial disruption; b) Particulate uptake from the intestinal lumen by M cells in the mucosa, thus overtaxing the immune system; e) Mesenteric microvascular permeability, thus reducing selective barriers to trans-vascular exchange; d) Increases heart rate but decreases heart rate variability, both markers of stress. 2. Determine whether dietary vitamin E and/or lipoic acid reduce the deleterious effects of ultrasound as demonstrated in Aim 1. Production of reactive oxygen species (ROS) will be assessed using a fluorescent probe; epithelial sloughing and mucosal mast cell degranulation by microscopy. Lack of selective exclusion of foreign particles by the M cells will be tested by orally administering polystyrene particles and measuring their concentrations in Peyer's patches and lymph nodes. Microvascular endothelial leakage and mesenteric mast cell degranulation will be assessed using intravital epifluorescence microscopy and image analysis. The effects of noise-induced stress on heart rate, heart rate variability and cardiac performance will be determined in conscious, freely moving rats by radiotelemetry. Rat behavior, another indicator of stress, will be assessed by videotaping pairs of rats in their cages before and after ultrasound.